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Recent Studies Recapped

By Suzanne D. Vernon, PhD

Lower Blood Pressure in CFS
Blood pressure is the force exerted on our blood vessels so that blood can be effectively circulated throughout our body. One of the most consistent observations in CFS patients is dysfunction of the autonomic nervous system (ANS) which controls blood pressure and heart rate, among other bodily functions. A unique study published by Newton et al, in the journal Psychosomatic Medicine measured the blood pressure and heart rate of CFS patients during the day and night.

The investigators enrolled 38 CFS subjects (as defined by the 1994 Fukuda criteria) and two control groups: 47 primary biliary cirrhosis subjects (an autoimmune disorder accompanied by severe fatigue) and 120 healthy persons. They monitored blood pressure and heart rate every 30 minutes from 7:00 a.m. until 10:00 p.m. and every 60 minutes between 10:00 p.m. and 7:00 a.m. They determined that the 24-hour systolic blood pressure and mean arterial pressure was significantly lower in CFS patients compared to the control groups. However, CFS patients had significantly lower diastolic blood pressure and mean arterial pressure during the night. This lower nighttime blood pressure could affect diurnal blood pressure.

While it is not clear whether lower blood pressure in CFS patients causes the fatigue, it is known that lower pressure will affect the amount of blood and oxygen that gets delivered to tissues (e.g., brain and muscle). The authors suggest that increasing blood pressure – targeting mechanisms that affect nighttime and diurnal blood pressure – may be a potential therapeutic approach in CFS patients with an autonomic phenotype and propose a randomized, placebo-controlled trial of agents such as midodrine.

Newton JL, Sheth A, Shin J, Pairman J, Wilton K, Burt JA, Jones DE.  Lower ambulatory blood pressure in chronic fatigue syndrome.  Psychosom Med. 2009 Apr;71(3):361-5.

Lumpers Versus Splitters
There are several medically unexplained illnesses that are characterized primarily by fatigue and other symptoms including CFS, fibromyalgia and irritable bowel syndrome (IBS). Some in the medical and scientific communities believe that syndromes that share the same symptoms should be lumped under the term “functional somatic syndromes,” while others believe that these disorders are distinct and should be classified as separate conditions (as they are now). In a paper published in the April issue of the journal Psychological Medicine, Hamilton et al, looked for risk markers that were either shared or unique to CFS and IBS to determine if these disorders should be lumped together or split apart.

This study used data from the General Practice Research Database in the United Kingdom, the largest primary care database in the world. The investigators identified 4,388 “fatigue syndrome” (CFS/ME and post-viral fatigue syndrome) patients with complete records for the three years prior to diagnosis. Two control groups were identified with 4,388 subjects each; one group was diagnosed with IBS and the other was comprised of patients seeing their provider for reasons other than these illnesses. They used this database to find possible risk, triggering and causal factors for CFS and IBS by looking at rates of allergy, infection, depression, immunization, and childbirth before onset, near onset and after onset of the illness, as well as other general information from the medical histories.

Not surprisingly, the investigators validated previous findings that fatigue syndromes are heterogeneous and that CFS and post-viral/post-infection fatigue have distinct predisposing and possible causal triggers. CFS and IBS were found to share predisposing risk markers including allergy, menstrual symptoms and immunization. CFS was more similar to IBS than was post-viral/post-infection fatigue, providing further evidence for the importance of identifying CFS subtypes. The authors conclude that the same risk markers predispose patients to develop fatigue syndromes and IBS, but specific factors trigger the specific illnesses. One novel finding was that women with CFS and IBS had lower rates of childbirth compared to the other groups, suggesting that child birth may possibly offer some protective factors for CFS and IBS.

This study suggests that CFS and post-viral/post-infection fatigue should be considered as separate conditions and that the ICD-10 taxonomy that currently classifies CFS and post-viral/post-infection together should be revised accordingly.

The authors acknowledge that they relied only on the treating physicians’ records to record diagnoses and information about the patients’ medical histories; no confirming tests or specific criteria were used to challenge the accuracy of these records. The size of the database and patient/control cohorts is the study’s primary strength.

Hamilton WT, Gallagher AM, Thomas JM, White PD.  Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study in primary care.  Psychol Med. 2009 Apr 15:1-9.

Probiotic Treatment Shows Some Relief for CFS
Research has shown that patients with CFS have some alteration of the intestinal microbial flora, and other studies have shown that non-disease causing gut bacteria might influence mood-related symptoms. This study randomized 39 CFS patients to receive either the probiotic lactobacillus casei or an identical-looking placebo for eight weeks. Four subjects withdrew, two from each group. They collected data using the Beck Depression Inventory, the Beck Anxiety Inventory and stool samples at the evaluation phase and after the eight-week treatment period.

Stool samples were evaluated for a change in the fecal total aerobes, anaerobes and total Bifidobacteria and Lactobacillus. In the placebo group, only 37.5% of subjects showed an increase in Bifidobacteria and 43.8% in Lactobacillus compared to 73.7% and 73.7% in the treatment group, respectively. An increase in the fecal Bifidobacteria level is considered by the investigators to be positive sign, since levels have been reported to be low in CFS, and Bifidobacteria is generally associated with a healthy colonic environment. The treatment group also showed improvement in the anxiety scores, but not depression scores.

The authors acknowledge that it is entirely possible that their results are a consequence of improved gut structure and function of a healthy intestinal biofilm restored by the lactobacillus casei probiotic. They suggest that follow-up studies with probiotics should further examine specific gut microbes, intestinal structure and function as well as physiological markers associated with anxiety and depression. These may include inflammatory cytokines and other immune chemicals, blood tryptophan levels and urinary metabolites of neurotransmitters.

Studies such as the one being conducted by Dr. Sanjay Shukla and his collaborators at the Marshfield Clinic Foundation, funded by the CFIDS Association of America, will improve our understanding of the role of gut permeability, microbial flora and probiotics in CFS.

Rao AV, Bested AC, Beaulne TM, Katzman MA, Iorio C, Berardi JM, and Logan AC. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathology. 2009; 1: 6.

Abstracts for Two Other Studies of Note:

Functional Neuroimaging of Fatigue
Deluca J, Genova HM, Capili EJ, Wylie GR. Physical Medicine and Rehabilitation Clinics of North America. 2009 May;20(2):325-337

Recent studies employing functional neuroimaging provide new insights into the elusive construct of fatigue. Studies have been conducted primarily in persons with multiple sclerosis (MS) and chronic fatigue syndrome (CFS). These studies outline the key role of the basal ganglia and frontal lobes in understanding the neural mechanisms associated with fatigue. The lack of a relationship between self-reported fatigue and objectively measured fatigue is outlined, and new functional imaging paradigms may lead to significant advances in relating cognitive fatigue to functional cerebral activity.

Health of U.S. Veterans of 1991 Gulf War: A follow-up survey in 10 years
Kang HK, Li B, Mahan CM, Eisen SA, Engel CC. Journal of Occupational and Environmental Medicine. 2009 Apr;51(4):401-10.

OBJECTIVE: To assess periodically the health status of a cohort of 1991 Gulf War veterans by comparing various health outcomes with those of their military peers who were not deployed to the Gulf. METHODS: We conducted a follow-up health survey to collect health information among population-based samples of 30,000 veterans (15,000 Gulf War veterans and 15,000 Gulf Era veterans) using a structured questionnaire. RESULTS: Gulf veterans reported significantly higher rates of unexplained multi-symptom illness, chronic fatigue syndrome-like illness, posttraumatic stress disorder, functional impairment, health care utilization, a majority of selected physical conditions and all mental disorders queried during the survey than did Gulf Era veteran controls. CONCLUSIONS: Fourteen years after deployment, 1991 Gulf War veterans continue to report a higher prevalence of many adverse health outcomes, compared with Gulf Era veterans.

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